Developmental mechanisms of adrenal cortex formation and their links with adult progenitor populations

Oikonomakos, Ioannis; Arachchige, Lahiru Chamara Weerasinghe; Schedl, Andreas

doi:10.1016/j.mce.2021.111172

Cited by 6 publications

(2 citation statements)

References 123 publications

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“…Finally, the innermost zona reticularis produces androgens (androstenedione and dehydroepiandrosterone—DHEA) in humans, but is absent in mice. Intense research has focused on the ability of the adrenal cortex to regenerate [ 9 ] and to regularly self-renew thanks to resident stem cell populations in the outer cortex, reviewed recently in [ 10 , 11 ]. Notably, the rate and capacity of self-renewal as well as several other physiological parameters of the adrenal cortex are markedly sexually dimorphic, owing mostly to gonadal steroid signaling (although genetic factors cannot be excluded).…”

Section: Introductionmentioning

confidence: 99%

The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease

Lyraki

Schedl

2021

IJMS

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Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy and sex hormone replacement experiments in mice have shed some light onto the molecular basis of sexual dimorphism in the adrenal cortex. Indeed, it has been shown that gonadal hormones influence many aspects of adrenal physiology, ranging from stem cell-dependent tissue turnover to steroidogenesis and X-zone dynamics. This article reviews current knowledge on adrenal cortex sexual dimorphism and the potential mechanisms underlying sex hormone influence of adrenal homeostasis. Both topics are expected to contribute to personalized and novel therapeutic approaches in the future.

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Section: Introductionmentioning

confidence: 99%

The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease

Lyraki

Schedl

2021

IJMS

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“…The adrenal gland is a steroidogenic organ essential for homeostasis in mammals, and its formation is a complex process during embryonic development 1 – 3 .…”

Section: Introductionmentioning

confidence: 99%

Conditional disruption of Nr5a1 directed by Sox9-Cre impairs adrenal development

Tagami,

Ikeda,

Ishizuka

et al. 2024

Sci Rep

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The current study aimed to investigate the effect of Sox9-Cre-directed Nr5a1-conditional knockout (Sox9-Cre;Nr5a1flox/flox) on adrenal development. We showed that SOX9 is expressed by adrenocortical cells at E10.5–E11.5 but is extinguished no later than E12.5. The number of adrenocortical cells significantly reduced in Sox9-Cre;Nr5a1flox/flox mice while the number of cleaved caspase 3-positive cells increased compared to that in the controls at E11.5–E12.5, when the adrenal primordium (AP) is about to expand. This indicated that fetal adrenocortical cells are lost via apoptosis due to Nr5a1 ablation by E12.5. Both medulla formation and encapsulation were perturbed, accompanied by a smaller AP size, in Sox9-Cre;Nr5a1flox/flox mice during embryonic development. Adult Sox9-Cre;Nr5a1flox/flox adrenals were hypoplastic and exhibited irregular organization of the medulla with aberrant sex differentiation in the X zone. Additionally, there were histologically eosin-negative vacuolated cells, which were negative for both the X-zone marker 20αHSD and the steroidogenesis marker 3βHSD at the innermost cortex of Sox9-Cre;Nr5a1flox/flox adrenals. Although Nr5a1+/− adrenals were hypoplastic, a small number of chromaffin cells were properly located in the center, having normal sex differences in the X-zone. The results collectively provided in-vivo evidence that Nr5a1 plays a critical role in AP expansion and subsequent adrenal development.

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